Paclitaxel/cemiplimab/fianlimab is a highly effective combination as neoadjuvant therapy in both triple-negative breast cancer (TNBC) and HR-positive/HER2-negative breast cancer. In addition, the ImPrint signature identifies patients with the greatest benefit from checkpoint inhibitor-based therapy, results from I-SPY 2 showed.
Addition of anti-PD-1 therapy to neoadjuvant chemotherapy has shown to significantly improve the pathologic complete response (pCR) and event-free survival in patients with TNBC . In melanoma, addition of an anti-LAG-3 antibody to anti-PD-1 therapy has shown to significantly improve progression-free survival . The neoadjuvant I-SPY 2 trial (NCT01042379) evaluated the efficacy and safety of the addition of the anti-PD-1 antibody cemiplimab plus the anti-LAG-3 antibody fianlimab to neoadjuvant treatment with paclitaxel. Prof. Claudine Isaacs (Georgetown University Medical Center, DC, USA) presented the results .
A total of 76 patients with HER2-negative, treatment-naïve breast cancer received neoadjuvant treatment with paclitaxel/cemiplimab/fianlimab for 12 weeks; 350 patients treated with paclitaxel alone served as a control. Addition of cemiplimab/fianlimab to paclitaxel increased the pCR rate: 44% versus 21% (all patients), 53% versus 29% (TNBC), and 36% versus 14% (HR-positive/HER2-negative). In addition, the residual cancer burden class was downshifted across all subtypes. RCB 0/1 class was 37% in the control arm versus 64% in the study arm in all patients, 48% versus 70% for TNBC patients, and 29% versus 60% for HR-positive/HER2-negative patients.
ImPrint, a 53-gene signature of neoadjuvant immunotherapy response, has recently been developed . In the I-SPY-2 trial, a positive ImPrint score was able to identify patients with the greatest benefit from checkpoint inhibitor-based therapy. The pCR rate in TNBC patients with a positive ImPrint score was 82% when treated with paclitaxel/cemiplimab/fianlimab compared with 32% in TNBC patients with a negative ImPrint score. The pCR rate in HR-positive/HER2-negative patients with a positive ImPrint score was 91% when treated with paclitaxel/cemiplimab/fianlimab compared with 28% in HR-positive/HER2-negative patients with a negative ImPrint score. Addition of fianlimab and cemiplimab to paclitaxel was associated with an increased incidence of immune-related adverse events as well as 3 cases (5%) of type 1 diabetes.
“Paclitaxel/cemiplimab/fianlimab is a highly-effective combination for neoadjuvant therapy in both TNBC and HR-positive/HER2-negative breast cancer,” concluded Prof. Isaacs. “In addition, the ImPrint signature identified patients with the greatest benefit from checkpoint inhibitor-based therapy.”
- Schmid P, et al. N Engl J Med 2022;386:556–567.
- Tawbi HA, et al. N Engl J Med. 2022;386:24–34.
- Isaacs C, et al. Evaluation of anti-PD-1 cemiplimab plus anti-LAG-3 REGN3767 in combination with paclitaxel in early-stage, high-risk HER2-negative breast cancer: results from the Neoadjuvant I-SPY 2 trial. Abstract GS5-03, SABCS 2022, 6–10 December, San Antonio, TX, USA.
- Mittempergher L, et al. J Clin Oncol. 2022;40(suppl):514–514.
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Table of Contents: SABCS 2022
Letter from the Editor
Racial disparity in the tumour microenvironment
Chemo-endocrine therapy worse for cognition than endocrine therapy alone
Early-Stage Breast Cancer
Anti-PD-1/anti-LAG-3 combination highly effective in HER2-negative breast cancer
MammaPrint test predictive for benefit of extended endocrine therapy
HR-positive/HER2-positive Breast Cancer: Trastuzumab-Deruxtecan
Trastuzumab deruxtecan effective in both second-line and neoadjuvant setting
HR-positive/HER2-negative Advanced Metastatic Breast Cancer
Benefit of adjuvant abemaciclib continues to deepen at longer follow-up
First-line ribociclib plus endocrine therapy outperforms combination chemotherapy
Treatment options beyond CDK4/6 inhibition
Triple-Negative Breast Cancer
Baseline CTC count can guide first-line treatment in HR-positive/HER-negative metastatic breast cancer
ZNF689 deficiency promotes intratumour heterogeneity and resistance to immune checkpoint blockade in TNBC
Oestradiol represses anti-tumoural immune response to promote progression of brain metastases
Basic and Translational Research
Resistance to CDK4/6 inhibitors is likely due to expansion of pre-existing resistant clones
Germline pathogenic variants for breast cancer also increase contralateral breast cancer risk
Low-dose tamoxifen still prevents recurrence from non-invasive breast cancer
Endocrine interruption to pursue pregnancy does not impact short-term disease in breast cancer
Mixed data: AMG 510 in tumours with KRASG12C